ZA200404749B - Methods of treating bacterial infections in dogs and cats - Google Patents
Methods of treating bacterial infections in dogs and cats Download PDFInfo
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- ZA200404749B ZA200404749B ZA200404749A ZA200404749A ZA200404749B ZA 200404749 B ZA200404749 B ZA 200404749B ZA 200404749 A ZA200404749 A ZA 200404749A ZA 200404749 A ZA200404749 A ZA 200404749A ZA 200404749 B ZA200404749 B ZA 200404749B
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- South Africa
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- composition
- substance
- dog
- cat
- pharmaceutically acceptable
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- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- WYUSVOMTXWRGEK-HBWVYFAYSA-N cefpodoxime Chemical compound N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC)C(O)=O)C(=O)C(=N/OC)\C1=CSC(N)=N1 WYUSVOMTXWRGEK-HBWVYFAYSA-N 0.000 description 1
- 229960005090 cefpodoxime Drugs 0.000 description 1
- JFPVXVDWJQMJEE-IZRZKJBUSA-N cefuroxime Chemical compound N([C@@H]1C(N2C(=C(COC(N)=O)CS[C@@H]21)C(O)=O)=O)C(=O)\C(=N/OC)C1=CC=CO1 JFPVXVDWJQMJEE-IZRZKJBUSA-N 0.000 description 1
- 229960001668 cefuroxime Drugs 0.000 description 1
- VUFGUVLLDPOSBC-XRZFDKQNSA-M cephalothin sodium Chemical compound [Na+].N([C@H]1[C@@H]2N(C1=O)C(=C(CS2)COC(=O)C)C([O-])=O)C(=O)CC1=CC=CS1 VUFGUVLLDPOSBC-XRZFDKQNSA-M 0.000 description 1
- UTBIMNXEDGNJFE-UHFFFAOYSA-N collidine Natural products CC1=CC=C(C)C(C)=N1 UTBIMNXEDGNJFE-UHFFFAOYSA-N 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 150000004292 cyclic ethers Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000004985 dialkyl amino alkyl group Chemical group 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 125000006264 diethylaminomethyl group Chemical group [H]C([H])([H])C([H])([H])N(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 230000007813 immunodeficiency Effects 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 125000000686 lactone group Chemical group 0.000 description 1
- 239000010410 layer Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 230000002906 microbiologic effect Effects 0.000 description 1
- ACTNHJDHMQSOGL-UHFFFAOYSA-N n',n'-dibenzylethane-1,2-diamine Chemical compound C=1C=CC=CC=1CN(CCN)CC1=CC=CC=C1 ACTNHJDHMQSOGL-UHFFFAOYSA-N 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 125000005633 phthalidyl group Chemical group 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
- 229960004919 procaine Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 125000003638 stannyl group Chemical group [H][Sn]([H])([H])* 0.000 description 1
- GFYHSKONPJXCDE-UHFFFAOYSA-N sym-collidine Natural products CC1=CN=C(C)C(C)=C1 GFYHSKONPJXCDE-UHFFFAOYSA-N 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
- A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
- A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
- A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
METHODS OF TREATING
BACTERIAL INFECTIONS IN DOGS AND CATS
The invention described herein relates to the treatment of a range of bacterial infections in companion animals, in particular cats and dogs, with a B-lactam derivative, compound of Formula |. The invention is also directed to pharmaceutical compositions of a compound of Formula 1.
NOR?
HoH
Ons Vs s : :
HoN ©
COR’
BACKGROUND OF INVENTION p-Lactam antibiotics, such as penicillins and cephalosporins, have been known for some time and are the subject of many review articles. See, for example,
Harvey, R.G., Hunter, P.A. The properties and use of penicillins in the veterinary field, with special reference to skin infections in dogs and cats. Veterinary Dermatology, 10:3, September 1999; Mason, 1.S., Kietzmann, M. Cephalosporins — pharmacological basis of clinical use in veterinary dermatology. Veterinary
Dermatology, 10:3, September 1999; and the references therein.
A number of cephalosporin derivatives, including several incorporating a cyclic ether moiety at the 3-position, were disclosed in International Patent
Application publication number WO 92/01696 and by Bateson et al in The Journal of
Antibiotics, Feb.1994, vol.47, no.2, at pages 253-256. Various mouse data are also disclosed in the latter paper. A process for preparing the cephalosporins is described in EP1178049A1. These publications are herein incorporated in their entirety. .
In one aspect, the invention is directed to a pharmaceutical composition for treating periodontal diseases in a dog or cat caused by bacterial infections comprising a therapeutically effective amount of a compound of Formula |,
NOR? £H H s : i =O Gy
HN ©
COR! wherein R'is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H, and R?is C4 alkyl, and a pharmaceutical diluent : or carrier. in a preferred embodiment, the pharmaceutically acceptable cation salt is
Na‘, K' or Li". in a second aspect, the invention is directed to a pharmaceutical composition for treating opportunistic bacterial infections resulting from (a) a compromised or diminished immunological system, (b) Feline Immunodeficiency Virus (FIV) or (C) cancer chemotherapy in or on a dog or cat comprising a therapeutically effective amount of a compound of Formula |,
NOR?
ON Wl IAS
HN °
COR! wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H, and R? is C4 alkyl, and a pharmaceutical diluent or carrier.
In a third aspect, the invention is directed to a pharmaceutical composition for treating a disease or condition caused by a bacterial infection in a dog or cat comprising a therapeutically effective amount of a compound of Formuia |,
NOR? : 4 8
ES)
HN © oR’ wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO-H, and R2is C4 alkyl, and a pharmaceutical diluent or carrier, with the proviso that if the pharmaceutically acceptable cation sait is Na, Li orK, R%is not methyl.
In a preferred embodiment, the disease or condition is a skin, soft tissue or urinary tract bacterial infection.
In another embodiment, R' is H, an alkaline metal, an alkaline earth metal, ammonium, benzyl, p-methoxybenzyl, benzoylmethyl, p-nitrobenzyl, 4-pyridylmethyl, 2,2,2-trichloroethyl, 2,2,2-fribromoethyi, t-butyl, t-amyl, allyl, diphenylmethyl, triphenyimethyl, adamantyl, 2-benzoyloxyphenyl, 4-methylthiophenyl, tetrahydrofur-2- yi, tertahydropyran-2-yl, pentachlorophenyl, acetonyl, p-toluenesulphonylethyl, methoxymethyi, a silyl, stannyl or phosphorus-containing group, an oxime radical of formula -N=CHR?® where R® is aryl or heterocyclyl, or an in vivo hydrolysable ester radical.
In a preferred embodiment, the compound of formula | is the Z-isomer.
In another preferred embodiment, R'is H, Na* or CH,OCOC(CHy)s).
In a more preferred embodiment, R is H or CO,CH,OCOC(CHa)s) and R? is methyl. in another embodiment, the pharmaceutical composition further comprises one or more agents used in the treatment or prophylaxis of disease or in the reduction or suppression of symptoms of such disease.
In a preferred embodiment, one or more of the agents are selected from antiparasitics, antihistamines, antifungals, antibacterials, anti-inflammatories, steroids, antipruritic agents,dietary supplements or emollients.
In a further preferred embodiment, the antiparasitics are selected from aryipyrazoles, avermectins, milbemycins, organophosphates or pyrethroids; the antihistamines are selected from chlorpheniramine, trimeprazine, diphenhydramine or doxylamine; the antifungals are selected from fluconazole, ketoconazole, itraconazole, griseofulvin or amphotericin B; the antibacterials are selected from enroflaxacin, marbofioxacin, ampicillin or amoxycillin; the anti-inflammatories are selected from prednisolone, betamethasone, dexamethasone, carprofen or ketoprofen; and the dietary supplement is gamma-iinoleic acid.
In a fourth aspect, the invention is directed to a method of treating periodontal disease or an opportunistic bacterial infection in or on a dog or cat, resulting from (a) a compromised or diminished immunological system, (b) Feline Immunodeficiency
Virus (FIV) or (c) cancer chemotherapy in or on a comprising administrating a therapeutically effective amount of a compound of Formula
NOR?
HH
Ss :
TT Jd
HN ©
COR! wherein R'is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO.H, and R? is C14 alkyl, effective in treating such a condition.
In a preferred embodiment, the pharmaceutically acceptable cation salt is
Na’, K or Li".
In a fifth aspect, the invention is directed to a method of treating a disease or condition caused by a bacterial infection in oron a dog or cat comprising administrating a therapeutically effective amount of a compound of Formula |,
NOR?
H H s i on Hie
HN © cosR! wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO2H, and R? is C14 alkyl, and a pharmaceutical diluent or carrier, with the proviso that if the pharmaceutically acceptable cation salt is Na, Li or K, R? is not methyl, effective in treating such a condition.
In a preferred embodiment, the disease or condition is a skin, soft tissue or urinary tract bacterial infection.
In a more preferred embodiment, the composition is administered to the dog or cat in a single dose. in another preferred embodiment, the administration is subcutaneous.
In a preferred embodiment, the therapeutically effective amount of the "compound of Formula | is 4mg/kg to 12mg/kg.
In a more preferred embodiment, the method provides a duration of treatment activity of at least five days against susceptible pathogens.
In a preferable embodiment, the duration is at least 7 days.
In another embodiment, the method of treating a disease or condition caused by a bacterial infection in or on a dog or cat comprises administrating a therapeutically effective amount of the pharmaceutical composition described above.
In a sixth aspect, the invention is directed to a kit for treatment or prevention of a bacterial infection or a condition caused or complicated by a bacterial infection, in or on a dog or cat, comprising : : a) a pharmaceutical composition as described above; and b) instructions describing a method of using the pharmaceutical composition to treat a bacterial infection or a condition caused or complicated by a bacterial infection, in or on a dog or cat. in a seventh aspect, the invention is directed to a method for increasing acute or chronic injection-site toleration in a dog or a cat, comprising administering to a dog or a cat in need thereof a single dose of a therapeutically effective amount of a
Formula
NOR? 4H H s :
TH AA
HoN ©
OR" wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating COH, and R? is C4 alkyl, effective in treating such a condition.
The term “ammonium” as used herein means an ammonium moiety optionally substituted with C4 alkyl, optionally substituted by OH; or Cs cycloalkyl groups. For example, lower alkylamines may be triethylamine, hydroxy-lower alkylamines such as 2-hydroxyethylamine, bis-(2-hydroxyethyl) amine or tris(2-hydroxyethyl)-amine, cycloalkylamines such as dicyclohexylamine or with procaine, dibenzylamine, N,N- dibenzylethylene-diamine, 1-ephenamine, N-methylmorpholine, N-ethylpiperidine, N- benyzl-B-phenethylamine, dehydroabietylamine, N,N*-bisdehydro-abietylamine, ethylenediamine, or bases of the pyridine type such as pyridine, collidine, or quionoline, or other amines which have been used to form salts with known penicillins and cephalosporins. Other useful salts include lithium and silver salts. Salts within compounds of Formula | may be prepared by salt exchange in a conventional manner.
The term “in vivo hydrolysable ester group” means a pharmaceutically acceptable ester group that readily breaks down in the human body to leave the parent acid or its salt. Suitable ester groups of the type include those described in
Bateson et al. (EP0540609B1), hereby incorporated by reference in its entirety. In particular, examples of suitable in vivo hydrolysable ester groups include acyloxyalkyl groups such as acetoxymethyl, pivaloyloxymethyl, a-acetoxyethyl, a-pivaloyloxyethyl, 1-(cyclohexylcarbonyloxy)prop-1-yl, and (1 -aminoethyl)carbonyloxymethyl; alkoxycarbonyloxyalky! groups, such as ethoxycarbonyloxymethyl, a- ethoxycarbonyloxyethyl and propoxycarbonyloxyethyl; dialkylaminoalkyl, especially di-loweralkylamino alkyl groups such as dimethylaminomethyl, dimethylaminoethyl, diethylaminomethyl or diethylaminoethyt; 2-(alkoxycarbonyl)-2-alkenyl groups such as 2-(isobutoxycarbonyl)pent-2-enyl and 2-(ethoxycarbonyl)but-2-enyl; lactone groups such as phthalidyl and dimethoxyphthalidyl; and esters linked to a second B-lactam antibiotic or to a B-lactamase inhibitor. Preferably, the in vivo hydrolysable ester group is the pivaloyloxymethyl ester.
The term “pharmaceutically acceptable salts” of the carboxy group of the compound of Formula | include metal salts, e.g. aluminum, alkali metal salts such as sodium or potassium, especially sodium, alkaline earth metal salts such as calcium or magnesium, and ammonium or substituted ammonium salts.
The term “therapeutically effective amount” as used herein means the dose of a compound of Formula | effective in treating bacterial infections. The dose may vary depending upon the dog or cat patient, but generally is about 0.01 to 100 mg/kg of the subject animal's weight.
It was determined that the compounds of Formula 1, exhibit an unexpectedly long half-life in dogs and cats, especially in view of comparable antibiotics. For example, Table | lists well-known antibiotics and their respective half-lives in different mammals, such as in mice, rats, dogs and cats.
TABLE |: Half-life of Known Antibiotics
Cefpodoxime____ | 0.68 (PO) | T14(P0) __ |24(PO)
Ampiciin_____ | [0.84(M [064 (M)
Cefamandole los) [082(V)
Cefazolin | __ __loee(m) |11(V) [Cefuroxime | 0.32(SC) [04 (IM [0.93 (M)
Cephalordine — losgmy ~~ [o0o7(M
Cephalothin 0.208 (IM 0.4 (IM [1.06 (IM) [Cephadine | ~~ 10.82(PO 3.64 (PO
Enythromycin____[065(V) [127 (IV 72(V) [Oleandomycin__[0.7(V) [083(IV 1.53 (IV (Tyiosn | ~~ [04W) 124(V) (Cefpodoxime data from “Abstracts of the 1996 ICAAC”: Abstract 593. All other data compiled from: “CRC Handbook of Comparative Pharmacokinetics and
Residues of Veterinary Antimicrobials”, J. Edmond Riviere; Arthur L. Craigmill,
Stephen F. Sundiof CRC Press 1991; Routes of administration: "IV" - intravenous; "IM" = intramuscular; "PO" = per os; "SC" = subcutaneous)
Following administration of the compound of Formula |, wherein R' is
COC(CHa)s), R?is methyl and the oxime ether is in the Z-configuration, the half-life in the mouse and rat were determined, respectively, to be about 2.2 hours and about 3.0 hours, after per os administration. Unexpectedly, however, in dogs and cats, the half-life was in both cases dramatically increased, as is set forth in Table 2 below.
Table 2: Half-life of compound of formula | in Dogs and Cats
Species Formula |: Z-(methyl oxime Half-life [Spee _[Fode [Due [ERFmenioine | Fake
Do [WV [Took |Nelompourd®) [60d
Coc a N= A hall compound |B
Note [1] Dose expressed as corresponding free acid : i.e. R'=H. Concentrations measured with respect to the free acid.
EXPERIMENTAL DETAILS
1. Pharmacokinetics
Experiment 1: Intravenous Dog
A male dog was dosed intravenously with an aqueous solution of Compound
I. Blood plasma was sampled at times up to 28 days post dosing. Plasma samples were extracted and assayed to determine the concentration by both bioassay and
High Pressure Liquid Chromatography (“HPLC”) as follows: 1 mL of plasma (or standards of spiked dog plasma) were acidified to a pH of less than 3 with hydrochloric acid, then shaken with 26 mL of ethyl acetate. The layers were separated by centrifugation. 22 mL of the organic layer was transferred into a fresh container and 2.0 mL of 0.1 M phosphate buffer, pH of 7.0, was added.
After shaking and centrifugation, the aqueous phase was recovered and assayed.
Following processing, samples (and standards) were assayed by hole-in-the-plate microbiological bioassay on large plates (200 mL Mueller Hinton agar) seeded with
M. luteus. Samples were also assayed by HPLC (uBondapk —C18 column eluted with acetonitrile- 0.05M sodium acetate pH 5.0, 15:85, with UV detection at 256nm).
Good agreement was obtained between the two assay methods, and the half-life was calculated from bioassay results using standard pharmacokinetic methods.
Claims (42)
1. A pharmaceutical composition for treating periodontal diseases in a dog or cat caused by bacterial infections comprising a therapeutically effective amount of a compound of Formula l, NOR? H H H £ EF NN Nag: : pS S > 3 = i pul 0 I HN © OR! wherein R'is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H, and R? is C14 alkyl, and a pharmaceutical diluent or carrier.
2. A pharmaceutical composition according to Claim 1, wherein the pharmaceutically acceptable cation salt is Na®, K™ or Li*.
3. A pharmaceutical composition for treating opportunistic bacterial infections resulting from (a) a compromised or diminished immunological system, (b) Feline Immunodeficiency Virus (FIV) or (c) cancer chemotherapy inoron a dog or cat comprising a therapeutically effective amount of a compound of Formula |, NOR? H H s : H y=—=N I ° 1 HN © OR! wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H, and R? is Cis alkyl, and a pharmaceutical diluent or carrier.
4. A pharmaceutical composition for treating a disease or condition caused by a bacterial infection in a dog or cat comprising a therapeutically effective amount of a compound of Formula |, NOR? H 8 Ss SI ] HA HN © COsR' wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO;H, and R? is C4 alkyl, and a pharmaceutical diluent or carrier, with the proviso that if the pharmaceutically acceptable cation salt is Na, Li or K, R?is not methyl.
5. A pharmaceutical composition according to Claim 4, wherein the disease or condition is a skin, soft tissue or urinary tract bacterial infection.
6. A pharmaceutical composition according to Claims 1, 2, 3, 4 or 5, wherein R'is H, an alkaline metal, an alkaline earth metal, ammonium, benzyl, p- methoxybenzyl, benzoyimethyl, p-nitrobenzyl, 4-pyridyimethyl, 2,2,2-trichloroethyl, 2,2,2-tribromoethyl, t-butyl, t-amyl, allyl, diphenylmethyl, triphenylmethyl, adamantyl, 2-benzoyloxyphenyl, 4-methyithiophenyl, tetrahydrofur-2-yl, tertahydropyran-2-i, pentachlorophenyl, acetonyl, p-toluenesulphonylethyi, methoxymethyl, a silyl, stanny! or phosphorus-containing group, an oxime radical of formula -N=CHR® where R® is aryl or heterocyclyl, or an in vivo hydrolysable ester radical.
7. A pharmaceutical composition according to Claim 6, wherein the compound of formula | is the Z-isomer.
8. A pharmaceutical composition according to Claim 7, wherein R' is H, Na* or CH,OCOC(CHs)s).
9. A pharmaceutical composition according to Claims 1, 2 or 3, wherein R'is H or CO,CH,OCOC(CHs)s) and R? is methyl.
, PCT/IB02/04741
10. A pharmaceutical composition according to Claims 1, 2, 3, 4 or 5, further comprising one or more agents used in the treatment or prophylaxis of disease or in ‘ the reduction or suppression of symptoms of such disease.
11. A pharmaceutical composition according to Claim 10, wherein one or . 5 more of the agents are selected from antiparasitics, antihistamines, antifungals, antibacterials, anti-inflammatories, steroids, antipruritic agents, dietary supplements or emollients.
12. A pharmacetutical composition according to Claim 11, wherein the antiparasitics are selected from arylpyrazoles, avermectins, milbemycins, organophosphates or pyrethroids; the antihistamines are selected from chlorpheniramine, trimeprazine, diphenhydramine or doxylamine; the antifungals are selected from fluconazole, ketoconazole, itraconazole, griseofulvin or amphotericin B; the antibacterials are selected from enroflaxacin, marbofloxacin, ampicillin or amoxycillin; the anti-inflammatories are selected from prednisolone, betamethasone, dexamethasone, carprofen or ketoprofen; and the dietary supplement is gamma- linoleic acid.
13. Use of a compound of Formula NOR? H H s ; 8 9-oUNS HoN © COR! ) wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H and R? is C,., alkyl, in the manufacture of a medicament for treating periodontal disease or an opportunistic bacterial infection in or on a dog or cat, resulting from (a) a compromised or diminished immunological system, (b) Feline Immunodeficiency Virus (FIV) or (c) cancer chemotherapy. AMENDED SHEET
¢ * i PCT/IB02/04741
14. Use according to Claim 13, wherein the pharmaceutically acceptable cation salt is Na*,K* or Li".
15. Use of a compound of Formula |, NOR? yu : S : = THA HN © : cor’ wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H and R?is C,, alkyl, and : a pharmaceutical diluent or carrier, with the proviso that if the pharmaceutically acceptable cation salt is Na, Li or K,R? is not methyl, in the manufacture of a medicament for treating a disease or condition caused by a bacterial infection in or on a dog or cat.
16. Use according to Claim 15, wherein the disease or condition is a skin, soft tissue or urinary tract bacterial infection.
17. Use according to Claims 13, 14, 15 or 16 wherein said medicament is administrable to the dog or cat in a single dose.
18. Use according to Claim 17, wherein administration is subcutaneous.
19. Use according to Claim 18, wherein an effective amount of the compound of Formula | is 4mg/kg to 12mg/kg.
20. Use according to Claim 19, wherein the duration of treatment activity of at least five days against susceptible pathogens is provided.
21. Use according to Claim 20, wherein the duration is at least 7 days.
22. Use of a composition according to Claim 9 in the manufacture of a medicament for treating a disease or condition caused by a bacterial infection in or on a dog or cat.
23. A kit for treatment or prevention of a bacterial infection or AMENDED SHEET
! sa ) PCT/IB02/04741 i 19 a condition caused or complicated by a bacterial infection, in or on a dog or cat, comprising: a) a pharmaceutical composition according to Claims 1, 2, 3, 4 or 5; and b) instructions describing a method of using the pharmaceutical composition to treat a bacterial infection or a condition caused or complicated by a bacterial infection, in or on a dog or cat.
24. A method of increasing acute or chronic injection-site toleration in a dog or a cat, comprising administering to a dog or a cat a single dose of an effective amount of a compound of Formula NOR? Wom . } g : Sp ony HoN on COR’ — wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H and R? is C,, alkyl.
25. Use of compound as defined in claim 24, wherein R'is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H and R?is C, 4 alkyl, in the manufacture of a medicament for increasing acute or chronic injection-site toleration in a dog or a cat.
26. A substance or composition for use in a method of treating periodontal disease or an opportunistic bacterial infection in or on a dog or cat, resulting from (a) a compromised or diminished immunological system, (b) Feline Immunodeficiency Virus (FIV) or (c) cancer chemotherapy, said substance or composition comprising a compound as defined in Claim 13 wherein R' is H, a pharmaceutically acceptable cation salt, or an Jin vivo hydrolysable group capable of generating CO,H and R? is C,, alkyl, and said method comprising administering a therapeutically effective amount of said substance or composition. AMENDED SHEET
. PCT/IB02/04741
27. A substance or composition for use in a method of treatment according to Claim 26, wherein the pharmaceutically acceptable cation salt is Na*, K* or Li*.
28. A substance or composition for use in a method of treating a disease or condition caused by a bacterial infection in or on a dog or cat, said substance or composition comprising a compound as defined in Claim 15 wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H, and R?is C,, alkyl, and a pharmaceutical diluent or carrier, with the proviso that if the pharmaceutically acceptable cation salt is Na, Li or K, R? is not methyl, and said method comprising administering a therapeutically effective amount of said substance or composition.
29. A substance or composition for use in a method of treatment according to Claim 28, wherein the disease or condition is a skin, soft tissue or urinary tract bacterial infection.
30. A substance or composition for use in a method of treatment according to Claims 26, 27, 28, or 29 wherein said substance or composition is administered to a dog or cat in a single dose.
31. A substance or composition for use in a method of treatment according to Claim 30, wherein administration is subcutaneous.
32. A substance or composition for use in a method of treatment according to Claim 31, wherein the therapeutically effective amount of said substance or composition is 4mg/kg to 12mg/kg.
33. A substance or composition for use in a method of treatment according to Claim 32, wherein the method provides a duration of treatment activity of at least five days against susceptible pathogens.
34. A substance or composition for use in a method of treatment according to Claim 33, wherein the duration is at least 7 days.
35. A substance or composition for use in a method of treating a disease or condition caused by a bacterial infection in or on a dog or cat, said substance or composition comprising a composition according AMENDED SHEET
- PCT/IBO2/04741 to Claim 9, and said method comprising administering a therapeutically effective amount of said substance or composition.
36. A substance or composition for use in a method for increasing acute or chronic injection-site toleration in a dog or a cat, said substance or composition comprising a compound as defined in Claim 24, wherein R' is H, a pharmaceutically acceptable cation salt, or an in vivo hydrolysable group capable of generating CO,H and R? is C,, alkyl, and said method comprising administering a therapeutically effective amount of said substance or composition in a single dose to a dog or a cat in need thereof.
37. A composition according to any one of Claims 1 to 12, substantially as herein described and illustrated.
38. A substance or composition for use in a method of treatment according to any one of claims 1 to 12, or 26 to 36, substantially as herein described and illustrated.
39. Use according to any one of Claims 13 to 22, or 25, substantially as herein described and illustrated.
40. A kit according to Claim 23, substantially as herein described and illustrated.
41. A method according to Claim 24, substantially as herein described and illustrated.
42. A new composition, a substance or composition for a new use in a method of treatment; a new use of a compound according to any one of Claims 13, or 15, or 24; a new use of a composition according to Claim 9; a new kit; or a new non-therapeutic method of treatment, substantially as herein described. AMENDED SHEET
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB0130694.3A GB0130694D0 (en) | 2001-12-21 | 2001-12-21 | Treatment |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ZA200404749B true ZA200404749B (en) | 2006-07-26 |
Family
ID=9928201
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| ZA200404749A ZA200404749B (en) | 2001-12-21 | 2004-06-15 | Methods of treating bacterial infections in dogs and cats |
Country Status (4)
| Country | Link |
|---|---|
| US (1) | US20030149013A1 (en) |
| KR (1) | KR20040065294A (en) |
| GB (1) | GB0130694D0 (en) |
| ZA (1) | ZA200404749B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR20170002619U (en) | 2016-01-13 | 2017-07-21 | 신준기 | Pliers |
-
2001
- 2001-12-21 GB GBGB0130694.3A patent/GB0130694D0/en not_active Ceased
-
2002
- 2002-11-12 US US10/292,145 patent/US20030149013A1/en not_active Abandoned
- 2002-11-13 KR KR10-2004-7009585A patent/KR20040065294A/en not_active Application Discontinuation
-
2004
- 2004-06-15 ZA ZA200404749A patent/ZA200404749B/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20040065294A (en) | 2004-07-21 |
| US20030149013A1 (en) | 2003-08-07 |
| GB0130694D0 (en) | 2002-02-06 |
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